European vs 2015-World Health Organization clinical molecular and pathological classification of myeloproliferative neoplasms

Table 10 World Health Organization-clinical molecular and pathological criteria for hypercellular essential thrombocythemia associated with primary megakaryocytic, granulocytic myeloproliferation caused by calreticulin mutations[78]

Clinical CM criteria JAK2 wild type PMGM	Pathological ECP criteria of CALR MGM
A1 No preceding or allied other subtype of myeloproliferative neoplasm PV, CML, MDS. The main presenting features is pronounced isolated thrombocythemia with platelet count around or above 1000 × 109/L	P1 PMGM and relative or absolute reduction of erythropoiesis and erythroid precursors. Abnormal dense clustering and increase in atypical medium sized, large to giant immature megakaryocytes containing bulbous (cloud-like) hypolobulated nuclei and definitive maturation defects
A2 Presence of CALR mutation and JAK2 wild type
C Clinical stages of CALR MGM	MF Grading RF, MF
C1 Early clinical stage: Hb > 12 g/dL, slight to moderate splenomegaly, thrombocytosis around or above 1000 × 109/L, normal LAP score	MF 0 Prefibrotic CALR MGM, no reticulin fibrosis RF 0/1
C2 Intermediate clinical stage: slight anemia Hb < 12 to > 10 g/dL, decreasing platelet count, splenomegaly, increased LDH and definitive tear drop erythrocytes	MF 1 Early fibrotic CALR MGM slight reticulin fibrosis RF 2
C3 Advanced stage: anemia Hb < 10 g/dL, tear drop erythrocytes, increased LDH, increased CD34+ cells, pronounced splenomegaly, normal or decreased platelet counts, leucocytosis or leukopenia	MF 2 Fibrotic CALR MGM increase RF grade 3 and slight to moderate collagen fibrosis
	MF 3 Advanced fibrotic CALR MGM with collagen fibrosis-osteosclerosis

The combination of A1 + A2 and P1 establishes calreticulin (CALR) ET and various clinical stages(C1, C2, C3) related to the degree of myelofibosis (MF). This entity has been defined as CMGM in the 1990 Bone Marrow Classification by Georgii et al[35] as the third MPD entity and as chronic idiopathic myelofibrosis false ET or prefibrotic or primary megakaryocytic granulocytic myeloproliferation in 2002 by Michiels and Thiele (Table 5)[91]. PMGM: Primary megakaryocytic, granulocytic myeloproliferation; RF: Reticulin fibrosis; CM: Clinical and molecular; PV: Polycythemia vera; MDS: Myelodysplatic syndrome; LAP: Leukocyte alkaline phosphatase; CML: Chronic myeloid leukemia; Hb: Hemoglobin; LDH: Lactodehydrogenase; MGM: Megakaryocytic granulocytic myeloproliferation.